Catalytic Asymmetric Dehydrogenative Si–H/X–H Coupling toward Si-Stereogenic Silanes

Abstract

Chiral organosilicon compounds bearing a Si-stereogenic center have attracted increasing attention in various scientific communities and appear to be a topic of high current relevance in modern organic chemistry, given their versatile utility as chiral building blocks, chiral reagents, chiral auxiliaries, and chiral catalysts. Historically, access to these non-natural Si-stereogenic silanes mainly relies on resolution, whereas their asymmetric synthetic methods dramatically lagged compared to their carbon counterparts. Over the past two decades, transition-metal-catalyzed desymmetrization of prochiral organosilanes has emerged as an effective tool for the synthesis of enantioenriched Si-stereogenic silanes. Despite the progress, these catalytic reactions usually suffer from limited substrate scope, poor functional-group tolerance, and low enantioselectivity. The growing demand for Si-stereogenic silanes with structural diversity has continued to drive the development of new practical methods for the assembly of these chiral molecules.

Five years ago, our research group embarked on a project aimed at developing a general catalytic approach that can unlock access to various functionalized Si-stereogenic organosilanes with high efficiency. This Account describes our laboratory’s endeavor in the exploration and development of catalytic asymmetric dehydrogenative Si–H/X–H coupling toward Si-stereogenic silanes. This approach features (1) readily accessible dihydrosilane starting materials; (2) diverse X–H (X═C, N, O, etc.) coupling partners; (3) platform transformable Si-stereogenic monohydrosilane products; and (4) high efficiency and atomic economy.

At the initial stage of the research, a biaryl dihydrosilane was selected as the model substrate to conduct an enantioselective intramolecular C–H/Si–H dehydrogenative coupling reaction. Rh/Josiphos catalytic system was found to be effective at the early stage of this process, while the final enantiocontrol was elusive. Mechanistic studies indicated that a rhodium silyl dihydride complex is the resting state in the catalytic cycle, which may undergo racemization of the Si-stereogenic center. Enlightened by the mechanistic investigations, two strategies, the tandem alkene hydrosilylation strategy and bulky alkene-assisted dehydrogenative strategy, were adopted to avoid racemization, delivering the corresponding Si-stereogenic 9-silafluorenes with excellent yields and enantioselectivities. Further enantioselective intramolecular C(sp²)–H or C(sp³)–H silylation gave access to a series of five-, six- and seven-membered Si-stereogenic heterocycles with high efficiency. Next, we extended the reaction to an intermolecular version, realizing asymmetric Si–H/C–H, Si–H/O–H, and Si–H/N–H dehydrogenative coupling reactions toward a variety of acyclic Si-stereogenic monohydrosilanes, silyl ethers, siloxanes, silanols, and silazanes. We also presented our endeavors to apply the resulting Si-stereogenic compounds, including further derivatization, polymerization, and chiroptical property investigations, which successfully introduced Si-stereocenters into bioactive molecules, polymers, and chiroptical materials. Lastly, based on the understanding of silyl metal species, we developed a new type of chiral silyl ligand that can be applied to enable an atroposelective intermolecular C–H/Si–H dehydrogenative coupling reaction. We anticipate that our research, including synthetic methodology, mechanistic insights, and property studies, will not only inspire the further development of chiral organosilicon chemistry but also contribute to the creation of novel chiral molecules to be applied in synthetic chemistry, medicinal chemistry, and materials science.